ArticleProceedings of the National Academy of Sciences of the United States of America2016
Early signaling dynamics of the epidermal growth factor receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
49 citing papers in PubMed, 93 citations in OpenAlex.
- Growth factor applications and clinical translation: advances and challenges.Annals of medicine · 2026Review
- Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.Nature communications · 2026Article
- Scalable phosphotyrosine enrichment with SH2 superbinder enables deep profiling of EGF responses.The EMBO journal · 2026Article
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- Kinase KEY1 controls pyrenoid condensate size throughout the cell cycle by disrupting phase separation interactions.Nature cell biology · 2026Article
- Benchmarking EGF signaling pathway inference using phosphoproteomics and kinase-substrate interactions.Nature communications · 2026Article
- Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap.Nature chemical biology · 2026Article
- Kinase KEY1 controls pyrenoid condensate size throughout the cell cycle by disrupting phase separation interactions.bioRxiv : the preprint server for biology · 2025Article
- Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity.Molecular cell · 2025Article
- R2HaPpY: Rapid-robust phosphotyrosine peptide enrichment using HaloTag-Src SH2 pY superbinder.bioRxiv : the preprint server for biology · 2025Article
- Signaling and transcriptional dynamics underlying early adaptation to oncogenic BRAF inhibition.Cell systems · 2025Article
- Identification of phosphatases that dephosphorylate the co-chaperone BAG3.Life science alliance · 2025Article
- Protein phosphatase-1 regulates the binding of filamin C to FILIP1 in cultured skeletal muscle cells under mechanical stress.Scientific reports · 2024Article
- Article
- Dissecting signaling regulators driving AXL-mediated bypass resistance and associated phenotypes by phosphosite perturbations.bioRxiv : the preprint server for biology · 2023Article
- Predictive data-driven modeling of C-terminal tyrosine function in the EGFR signaling network.Life science alliance · 2023Article
- A circuit for secretion-coupled cellular autonomy in multicellular eukaryotic cells.Molecular systems biology · 2023Article
- Mechanistic model of MAPK signaling reveals how allostery and rewiring contribute to drug resistance.Molecular systems biology · 2023Article
- Phosphoproteomics data-driven signalling network inference: Does it work?Computational and structural biotechnology journal · 2023Article
- Epigenetic reader BRD4 supports mycobacterial pathogenesis by co-modulating host lipophagy and angiogenesis.Autophagy · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Despite extensive study of the EGF receptor (EGFR) signaling network, the immediate posttranslational changes that occur in response to growth factor stimulation remain poorly characterized; as a result, the biological mechanisms underlying signaling initiation remain obscured. To address this deficiency, we have used a mass spectrometry-based approach to measure system-wide phosphorylation changes throughout the network with 10-s resolution in the 80 s after stimulation in response to a range of eight growth factor concentrations. Significant changes were observed on proteins far downstream in the network as early as 10 s after stimulation, indicating a system capable of transmitting information quickly. Meanwhile, canonical members of the EGFR signaling network fall into clusters with distinct activation patterns. Src homology 2 domain containing transforming protein (Shc) and phosphoinositol 3-kinase (PI3K) phosphorylation levels increase rapidly, but equilibrate within 20 s, whereas proteins such as Grb2-associated binder-1 (Gab1) and SH2-containing tyrosine phosphatase (SHP2) show slower, sustained increases. Proximity ligation assays reveal that Shc and Gab1 phosphorylation patterns are representative of separate timescales for physical association with the receptor. Inhibition of phosphatases with vanadate reveals site-specific regulatory mechanisms and also uncovers primed activating components in the network, including Src family kinases, whose inhibition affects only a subset of proteins within the network. The results presented highlight the complexity of signaling initiation and provide a window into exploring mechanistic hypotheses about receptor tyrosine kinase (RTK) biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.